The research proposed in this application involves the serological definition of rat Ia (Immune Response Associated) antigens, and studies on how these antigens affect the immune response. Projects are planned to determine whether Ia antigens are present on effector cells which cause experimental allergic encephalomyelitis, and whether anti-Ia sera can inhibit in vitro manifestations of Ir gene - controlled immune responses. The ability of anti-Ia sera to enhance the survival of transplanted hearts will also be studied. Several experiments involving anti-receptor site antibodies are proposed. We wish to determine whether tolerance to a weak transplantation antigen and unresponsiveness to myelin basic protein can be induced by such sera. Previous work on the genetics of response to the mouse Ea-1 erythrocyte antigens suggested that genetic complementation for suppressor cell activity may occur. We propose to test this hypothesis by cell transfer studies. A histocompatibility locus in rats has been described for which a very strong heterozygote advantage occurs. We propose to look for antisera to define these antigens, to study the transmission frequencies of the two alternative alleles, and to see whether this locus is linked to Ag-B.